The research proposed is an analysis of the biochemical basis of the developmental effects of lethal mutations in the T/t-complex, and a detailed study of the separate genetic factors that comprise lethal t-haplotypes. We will attempt to define serologically in more detail the distribution of specific cell surface T/t-antigens on pre- and post-implantation embryos, and on teratocarcinoma cell lines derived from T/t mutant mice, using our available conventional antisera and, we hope, monoclonal antibody reagents that we are trying to produce. The serological studies will be used as the basis for further biochemical investigations of the cell surface. These will include studies of the carbohydrate structure of T/t-antigens and their role in development, as well as attempts to isolate and characterize T/t-associated molecules by immunoprecipitation and two-dimensional gel analysis. We will analyze the fine structure of mutant factors in the T/t-complex by deletion mapping with four different deletions that cover different lengths of chromosome in the region between the centromere and a marker about 10 cM distal, and by recombinational analysis of naturally occurring t-haplotypes and their derivatives.